Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.

Publication Type:

Journal Article


Cell, Volume 184, Issue 11, p.2955-2972.e25 (2021)


Animals, Antibodies, Neutralizing, B-Lymphocytes, Broadly Neutralizing Antibodies, COVID-19, Dimerization, env Gene Products, Human Immunodeficiency Virus, Epitopes, Glycosylation, HIV Antibodies, HIV Infections, HIV-1, Humans, Immunoglobulin Fab Fragments, Macaca mulatta, Polysaccharides, Receptors, Antigen, B-Cell, SARS-CoV-2, Simian Immunodeficiency Virus, Spike Glycoprotein, Coronavirus, Vaccines


<p>Natural antibodies (Abs) can target host glycans on the surface of pathogens. We studied the evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylated HIV-1 envelope (Env) as a model antigen. 2G12 is a broadly neutralizing Ab (bnAb) that targets a conserved glycan patch on Env of geographically diverse HIV-1 strains using a unique heavy-chain (V) domain-swapped architecture that results in fragment antigen-binding (Fab) dimerization. Here, we describe HIV-1 Env Fab-dimerized glycan (FDG)-reactive bnAbs without V-swapped domains from simian-human immunodeficiency virus (SHIV)-infected macaques. FDG Abs also recognized cell-surface glycans on diverse pathogens, including yeast and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike. FDG precursors were expanded by glycan-bearing immunogens in macaques and were abundant in HIV-1-naive humans. Moreover, FDG precursors were predominately mutated IgMIgDCD27, thus suggesting that they originated from a pool of antigen-experienced IgM or marginal zone B cells.</p>